Careers-perspective interview
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Journal Article↗
Biomedical subjects
E Douville
Publications and source records attributed to E Douville.
EGF induced SOS phosphorylation in PC12 cells involves P90 RSK-2.
SOS, the guanine nucleotide exchange factor for Ras, becomes phosphorylated on serine and threonine residues following stimulation of cells with growth factors. These phosphorylations may play a role in negative feedback of Ras stimulation and have been shown to be mediated in part by the MAP kinases Erk-1 and Erk-2. Here we show that in addition to MAP kinase, a major mitogen activated kinase for SOS is p90 Rsk-2, a downstream target of MAP kinase. p90 Rsk-2 phosphorylates SOS in an in gel assay and also in solution in vitro. The ability of p90 Rsk-2 to phosphorylate SOS increases greatly following EGF treatment of PC12 cells and is blocked by expression of N17 Ras or treatment with the MEK inhibitor PD98059. Phosphopeptide mapping revealed that the sites phosphorylated by p90 Rsk-2 in vitro were also phosphorylated in intact cells in response to EGF treatment. Several major sites of in vivo phosphorylation correlated with p90 Rsk-2 phosphorylation sites rather than MAP kinase sites. It is therefore likely that p90 Rsk-2 plays an important role in the down regulation of the Ras activation pathway through SOS.
Amino Acid Sequence↗
Dual specificity kinases--a new family of signal transducers.
Phosphorylation/dephosphorylation reactions are one of the dynamic mechanisms through which cells modulate protein activity in response to environmental stimuli. The eukaryotic molecules which are responsible for the phosphorylation of serine, threonine and tyrosine residues appear to have co-ordinately evolved from simple prokaryotic enzymes which primarily respond to nutritional cues. In multicellular eukaryotes the complexity of data transfer greatly exceeds that of simple bacteria. The eukaryotic cell needs to exchange information with neighbouring and distant sister cells. Positional, nutritional and hormonal data are transmitted from the extracellular milieu across the plasma membrane and into the cytoplasm. In certain cases the signal must pass into the nucleus or other subcellular organelles where it is decoded and the proper cellular response initiated. All of these events have been shown to have a protein kinase component and it seems likely that in mammalian cells over 1,000 different kinase molecules have evolved to form the requisite signal transducing networks. In this review we describe a previously unappreciated family of protein kinases, the dual specificity or DSK kinases, which play important roles in the regulation of normal cellular growth and differentiation.
Animals↗